Astrocytic networks and gap junctional communication mediated by connexins (Cxs) have been repeatedly implicated in seizures, epileptogenesis, and epilepsy. However, the effect of seizures on Cx expression is controversial. The present study focused on the response of Cxs to status epilepticus (SE), which is in turn an epileptogenic insult. The expression of neuronal Cx36 and astrocytic Cx30 and Cx43 mRNAs was investigated in the brain of rats in the first day after pilocarpine-induced SE. In situ hybridization revealed a progressive decrease in Cx43 and Cx30 mRNA levels, significantly marked 24 h after SE onset in neocortical areas and the hippocampus, and in most thalamic domains, whereas Cx36 mRNA did not exhibit obvious changes. Regional evaluation with quantitative real-time-RT-PCR confirmed Cx43 and Cx30 mRNA downregulation 24 h after SE, when ongoing neuronal cell death was found in the same brain regions. Immunolabeling showed at the same time point marked a decrease in Cx43, microglia activation, and interleukin-1β induction in some microglial cells. The data showed a transient downregulation of astroglial Cxs in the cortical and thalamic areas in which SE triggers neurodegenerative events in concomitance with microglia activation and cytokine expression. This could potentially represent a protective response of neuroglial networks to SE-induced acute damage.

Copper homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones encoded by a group of genes collectively known as copper homeostasis genes (CHGs). In this work, analysis of The Cancer Genome Atlas database for somatic point mutations in colorectal cancer revealed that inactivating mutations are absent or extremely rare in CHGs. Using oligonucleotide microarrays, we found a strong increase in mRNA levels of the membrane copper transporter 1 protein [CTR1; encoded by the solute carrier family 31 member 1 gene (SLC31A1 gene)] in our series of colorectal carcinoma samples. CTR1 is the main copper influx transporter and changes in its expression are able to induce modifications of cellular copper accumulation. The increased SLC31A1 mRNA level is accompanied by a parallel increase in transcript levels for copper efflux pump ATP7A, copper metabolism Murr1 domain containing 1 (COMMD1), the cytochrome C oxidase assembly factors [synthesis of cytochrome c oxidase 1 (SCO1) and cytochrome c oxidase copper chaperone 11 (COX11)], the cupric reductase six transmembrane epithelial antigen of the prostate (STEAP3), and the metal‐regulatory transcription factors (MTF1, MTF2) and specificity protein 1 (SP1). The significant correlation between SLC31A1, SCO1, and COX11 mRNA levels suggests that this transcriptional upregulation might be part of a coordinated program of gene regulation. Transcript‐level upregulation of SLC31A1, SCO1, and COX11 was also confirmed by the analysis of different colon carcinoma cell lines (Caco‐2, HT116, HT29) and cancer cell lines of different tissue origin (MCF7, PC3). Finally, exon‐level expression analysis of SLC31A1 reveals differential expression of alternative transcripts in colorectal cancer and normal colonic mucosa.

In recent reports, ciliary neurotrophic factor (CNTF) has been implicated as an injury factor involved in regulating astrogliosis in the CNS. In this study, we used a rat oligodendroglial progenitor cell line that is highly responsive to CNTF to examine CNTF‐induced alterations that may play a role in activation of the glial fibrillary acidic protein (GFAP) gene. We determined that CNTF induces the transient translocation of Stat1α/p91 to the nucleus. This nuclear translocation was followed by GFAP promoter activation and an up‐regulation of GFAP mRNA and protein. Levels of CNTF‐α receptor mRNA, however, were unaffected by addition of the ligand. Transfection studies using an upstream 5′‐flanking, 1.9‐kb rat GFAP promoter linked to a luciferase reporter gene revealed CNTF‐induced transcriptional activation within 1 h of ligand exposure. Moreover, serial‐deleted constructs identified a distal (−1,857 to −1,546 bp) and a proximal (−384 to −106 bp) region as being important for CNTF‐induced GFAP promoter activation. These two regions showed a strong degree of overlap for CNTF‐ and serum‐induced activation of the GFAP gene. Analysis of the two regions revealed several cis‐elements that are thought to be involved in GFAP regulation and/or the regulation of other genes by members of the interleukin‐6 family of cytokines. Moreover, we are the first to report the presence of several putative CNTF‐responsive elements within our identified distal and proximal regions in the GFAP gene promoter.